Independent Prognostic Factor For Survival Research Articles

Prognostic value of lymph node features in patients diagnosed with stage IIIC endometrial adenocancer.

Our study investigated the lymph node (LN) features most affecting survival in endometrial adenocancer (EAC) patients with LN involvement. This retrospective study was based on a review of the records of patients diagnosed with EAC, who underwent hysterectomy and systematic retroperitoneal lymphadenectomy at the gynecologic oncology clinics of three centers between January 2009 and January 2019. A total of 120 stage IIIC endometrioid-type EAC patients were included in the study. The patients were divided into small (<10 mm) and large (≥10 mm) groups according to the size of the largest metastatic LN. Patients were divided into single and multiple metastasis groups according to the number of metastatic LNs. The patients were divided into pelvic and paraaortic groups according to the location of the metastatic LNs. The effects of prognostic factors on disease-free survival (DFS) and overall survival (OS) were evaluated by Cox regression analysis. Large-sized metastatic LNs were an independent prognostic factor for DFS (hazard ratio [HR] = 5.4, 95% confidence interval [CI]: 1.-26.2; P = 0.035) and OS (HR = 9.0, 95% CI: 1.1-68.0; P = 0.033). The number (P = 0.093 for DFS, P = 0.911 for OS) and location (P = 0.217 for DFS, P = 0.124 for OS) of metastatic LNs were not independent prognostic factors for DFS or OS. Large-sized metastatic LNs were an independent prognostic factor for survival in patients with stage IIIC EAC. Larger prospective studies including similar patient populations are required to verify these findings.

OPLAH Protein Expression Stratifies the Prognosis of Patients With Squamous Cell Carcinoma of the Esophagus.

Squamous cell carcinoma is one of the major subtypes of esophageal carcinoma, and the 5-year overall survival rate of esophageal squamous cell carcinoma patients who underwent curative treatment remains below 40%. We aimed to detect and validate the prognosticators of esophageal squamous cell carcinoma in patients who underwent radical esophagectomy. Comprehensive analysis of transcriptome and clinical data from The Cancer Genome Atlas revealed OPLAH as one of the differentially expressed genes between esophageal squamous cell carcinoma tissues and normal esophageal mucosa. OPLAH expression changes were significantly associated with a patient prognosis. OPLAH protein levels were further evaluated by immunohisto-chemistry in esophageal squamous cell carcinoma tissues (n=177) as well as in serum samples (n=54) using ELISA. OPLAH mRNA was significantly overexpressed in esophageal squamous cell carcinoma tissues compared to normal esophageal mucosa, and patients with high OPLAH mRNA expression have a significantly poorer prognosis, according to The Cancer Genome Atlas data. The high staining intensity of OPLAH protein in esophageal squamous cell carcinoma tissue clearly stratified patient prognosis. According to multivariable analysis, high OPLAH protein expression was an independent prognostic factor for survival after surgery. Pre-neoadjuvant chemotherapy serum OPLAH protein concentrations were significantly associated with clinical tumor depth and node positivity and, consequently, with advanced clinical stage. The serum OPLAH protein concentration was significantly decreased by neoadjuvant chemotherapy. OPLAH protein expression in cancerous tissue and serum may have clinical utility towards stratifying prognosis of patients with esophageal squamous cell carcinoma.

Identification of FKBP10 prognostic value in lung adenocarcinoma patients with surgical resection of brain metastases: A retrospective single-institution cohort study

ObjectiveTo explore the expression levels and clinical value of FKBP10 in lung adenocarcinoma brain metastases. DesignA retrospective single-institution cohort study. PatientsThe perioperative records of 71 patients with lung adenocarcinoma brain metastases who underwent surgical resection at the authors’ institution between November 2012 and June 2019 were retrospectively analyzed. MethodsThe authors evaluated FKBP10 expression levels using immunohistochemistry in tissue arrays of these patients. Kaplan-Meier survival curves were constructed, and a Cox proportional hazards regression model was used to identify independent prognostic biomarkers. A public database was used to detect FKBP10 expression and its clinical value in primary lung adenocarcinoma. ResultsThe authors found that the FKBP10 protein was selectively expressed in lung adenocarcinoma brain metastases. Survival analysis showed that FKBP10 expression (p = 0.02, HR = 2.472, 95% CI [1.156, 5.289]), target therapy (p < 0.01, HR = 0.186, 95% CI [0.073, 0.477]), and radiotherapy (p = 0.006, HR = 0.330, 95% CI [0.149, 0.731]) were independent prognostic factors for survival in lung adenocarcinoma patients with brain metastases. The authors also detected FKBP10 expression in primary lung adenocarcinoma using a public database, found that FKBP10 is also selectively expressed in primary lung adenocarcinoma, and affects the overall survival and disease-free survival of patients. LimitationsThe number of enrolled patients was relatively small and patients’ treatment options varied. ConclusionsA combination of surgical resection, adjuvant radiotherapy, and precise target therapy may benefit the survival of selected patients with lung adenocarcinoma brain metastases. FKBP10 is a novel biomarker for lung adenocarcinoma brain metastases, which is closely associated with survival time and may serve as a potential therapeutic target.

Computerized tomography-based first order tumor texture features in non-small cell lung carcinoma treated with concurrent chemoradiation: A simplistic and potential surrogate imaging marker for survival.

This study examines the role of tumor texture on computed tomography (CT) images as a complement to clinical prognostic factors in predicting survival in patients of non-small cell lung carcinoma (NSCLC) treated with radical chemo-radiation (CRT). A total of 93 patients with confirmed NSCLC treated with CRT accrued in a study approved by the institutional ethics committee were analyzed for CT-based radiomic features. Pretreatment CT images were used to contour the primary tumor and texture features were computed by the image filtration method to differentially highlight fine to coarse textures. Texture parameters included mean intensity, entropy, kurtosis, standard deviation, and mean positive pixel and skewness. Optimal threshold cut-off values of the above tumor texture features were analyzed. These features were explored as imaging biomarkers to predict survival using Kaplan-Meier and Cox proportional hazard model. Median follow-up of the entire cohort was 23.5 months [Interquartile range, IQR: 14-37] while for alive patients, median follow-up was 31 months (IQR: 23-49), 47 (50.6%) patients had died at the last follow-up. Univariate analysis revealed certain features like age, gender, response to therapy, and texture features like mean and kurtosis in CT images to be significant predictors of survival. In multivariate analysis, age (P = 0.006), gender (P = 0.004), treatment response (P< 0.0001), and two CT texture parameters: mean (P = 0.027) and kurtosis (P= 0.002) were independent prognostic factors of survival. CT-derived tumor heterogeneity (mean and kurtosis) complements clinical factors for predicting survival in NSCLC patients treated with CRT. Tumor radiomics warrants further validation as potential prognostic biomarkers for these patients.

Treatment outcomes of adjuvant radiotherapy in adrenocortical carcinoma - A 13-years experience from a tertiary care centre.

Adrenocortical carcinoma (ACC) is a rare and highly aggressive malignant neoplasm, usually diagnosed in advanced stage. Role and efficacy of adjuvant radiotherapy has not been well defined. The objective of this study is to describe the various clinical characteristics and prognostic factors affecting the survival of ACC along with the role radiotherapy on overall survival and relapse free survival. A retrospective analysis of 30 patients registered between 2007 and 2019 was carried out. The medical records containing clinical and treatment details were analysed. Data was analysed using SPSS 25.0. Survival curves were computed using Kaplan-Meier method. Univariate and multivariate analyses were performed to analyze the prognostic factors affecting the outcome. A p value of less than 0.05 was considered to be statistically significant. The median age of patients was 37.5 years (range, 5-72 years). 20 patients were females. Twenty-six patients had advanced stage (III/IV) disease while only four patients presented in early stage. Twenty-six patients underwent total adrenalectomy. Eighty three percent patients received adjuvant radiation therapy. The median follow up was 35.5 months (range, 7 monthss-132months). The estimated three- and 5-years overall survival (OS) was 67.2% and 23.3%, respectively. Capsular invasion and positive margins were the independent prognostic factors influencing both OS and relapse free survival (RFS). Out of 25 patients who received adjuvant radiation, only three patients had local relapse. ACC is a rare and aggressive neoplasm with majority of patients presenting in advanced stage. Surgical resection with negative margins remains the mainstay of treatment. Capsular invasion and positive margins are independent prognostic factors for survival. Adjuvant radiation reduces the risk of local relapse and is well tolerated. Radiation can be used effectively in adjuvant and palliative settings in ACC.

Increased NOTCH1 expression is associated with low survival in moderate/ poor differentiated human oral squamous cell carcinoma patients.

Notch deregulation has been reported in various types of cancers, including Oral squamous cell carcinomas (OSCCs). The role of Notch1 signaling in oral squamous cell carcinoma (OSCC) remains poorly understood. In this study, NOTCH1 was aberrantly expressed in human oral cancer tissues compared with that in normal marginal tissues and was associated with poor prognosis. The positive Notch 1 expression was significantly associated with poor tumor differentiation status. Kaplan-Meier survival curves revealed that elevated cytoplasmic NOTCH1 expression levels in OSCC patients were associated with poor overall survival. Moreover, multivariate COX proportional hazard models revealed that T N status, AJCC stage histological grade were independent prognostic factors for survival. Our result clearly demonstrates the oncogenic role of Notch1 in oral cancer and Notch1 may be a useful biomarker to target oral cancer patients.

The ALDH2, IGSF9, and PRDM16 Proteins as Predictive Biomarkers for Prognosis in Breast Cancer

IntroductionALDH2, IGSF9, and PRDM16 play crucial roles in regulating diverse cellular pathophysiologic functions. The current study was to evaluate the effect of the 3 proteins on clinicopathologic features and prognosis of patients with breast cancer. Materials and MethodsThe formalin-fixed and paraffin-embedded tissue specimens were collected from breast cancer patients by immunohistochemistry (IHC) were analyzed. ResultsOf the 216 patients enrolled, ALDH2 high expression was significantly correlated with the age (p = .040), larger tumor size (p = .001), LVI (p < .001), LNM (p < .001), advanced TNM staging (p < .001), PR (p = .027), HER2 status (p = .002), and molecular subtype (p = .003). IGSF9 low expression was significantly correlated with the LV1 (p = .024), LNM (p = .024), advanced TNM staging (p = .001). The low expression of PRDM16 was significantly correlated with age (p = .023), and LNM (p = .014). The A+I−P− expression (13.4%) were markedly correlated with lymphatic vessel invasion (LVI) (p < .001), lymph node metastasis (LNM) (p < .001), advanced TNM staging (p < .001). Furthermore, patients with A+I−P− expression had significantly advanced-stage breast cancer [stage III (72.4%) vs. (23.0%)]. Univariate and multivariate analysis identified variables (ie, larger tumor size, lymph node involvement, and A+I−P− expression) as independent prognostic factors for survival. ConclusionOur results reveal ALDH2 high expression, IGSF9 and PRDM16 low expression, A+I−P− expression was associated with advanced clinicopathological characteristics, and shorter OS and DFS in breast cancer patients. The 3 proteins may be potential prognosis markers and therapeutic targets for breast cancer patients.

Pre-Transplant Multiparameter Flow Cytometric Measurable Residual Disease in Acute Myeloid Leukemia As an Independent Prognostic Factor for Survival after Myeloablative Allogeneic Hematopoietic Cell Transplantation

Background Growing evidence suggests that multiparameter flow cytometric (MFC) measurable residual disease (MRD) assessment in acute myeloid leukemia (AML) should be used for risk stratification prior to allogeneic hematopoietic stem cell transplantation (alloHCT). We investigated the significance of MFC-MRD status in AML patients treated with myeloablative conditioning (MAC) alloHCT at transplant centers within the Polish Adult Leukemia Group (PALG). Methods All consecutive patients who underwent MAC alloHCT from HLA identical siblings (SD), family haploidentical donor, matched (10/10) unrelated donor (MUD), or mismatched (9/10) unrelated donor (mMUD) between January 2014 and May 2022 and for whom pre-transplant MFC-MRD was assessed were included in the analysis. MFC-MRD assessment has been routinely performed on bone marrow aspirates obtained before alloHCT since 2014 or as part of the PALG-AML1/2016 study protocol (NCT03257241) since 2018. Flow cytometry laboratory protocols were modified and unified by the cooperating laboratories according to the European LeukemiaNet recommendations in 2018. Residual disease at a level ≥0.1% was considered MRD(+). Results We analyzed 302 adult patients (median age 44 years, range 18-68) with AML in first (88%) or subsequent CR (12%) after intensive chemotherapy, including 81 patients (27%) transplanted between 2014-2017 and 221 (73%) transplanted between 2018-2022. Positive MRD status before alloHCT was detected in 143/302 pts (47%). The European LeukemiaNet (ELN) cytogenetic/genetic risk (Dohner 2010) was available in 290 of the 302 patients and was intermediate-II (Int-II)/high in 22%. Patients received MAC based on i.v. busulfan (84%), treosulfan (1%) or total body irradiation (15%) and graft from either SD (29%), haploidentical donor (9%), MUD (55%), or mMUD (7%). GvHD prophylaxis consisted of calcineurin inhibitor (CNI) combined with MTX (with or without ATG) or was based on post-transplant cyclophosphamide in transplants from haploidentical donor or mMUD. After the median follow-up of 30 months (range, 1-97), the 3-year LFS and OS for MRD(-) vs MRD(+) patients was 69% vs 54% (log-rank p=0.007), and 77% vs 62% (log-rank p=0.013), respectively. In multivariate Cox model, the independent adverse prognostic factors for LFS were MRD positive status (HR 1.53, 95%CI 1.03-2.25; p=0.0332), Int-II/high ELN risk (HR 1.87, 95%CI 1.24-2.84; p=0.0031), and age ≥ 45 years (HR 1.65, 95%CI 1.12-2.45; p=0.011). The same factors independently influenced OS [HR 1.59, 95%CI 1.01-2.48; p=0.0411; HR 1.67, 95%CI 1.03-2.71; p=0.0363, and HR 1.79, 95%CI 1.42-2.79; p=0.0109, respectively]. When the patients were classified according to the number of identified independent risk factors, the 3-year LFS and OS for patients with 0, 1, 2 and 3 risk factors was 75%, 68%, 51%, and 27% (p<0.0001) (Figure 1), and 81%, 77%, 57%, and 44%, respectively (p=0.0006). Conclusions Our findings confirm that pre-transplant residual disease at a ≥0.1% level assessed by MFC is an independent poor prognostic factor for both LFS and OS in AML patients treated with MAC alloHCT. As predicted, outcomes after MAC alloHCT were also independently influenced by ELN cytogenetic/genetic risk and age. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

PN3b as an independent risk factor for poor prognosis and peritoneal recurrence in Borrmann type IV gastric cancer: A retrospective cohort study

The clinicopathological features and surgical treatment strategies of Borrmann type IV gastric cancer (GC) remain controversial. Peritoneal metastasis is the most common recurrence pattern in patients with Borrmann type IV GC. Among 2026 gastric cancer between January 2009 and August 2019, 159 cases of Borrmann type IV GC were included in this study (7.8%). We retrospectively analyzed the clinicopathological characteristics and prognosis of these patients. Univariate and multivariate Cox proportional hazards were applied to identify independent prognostic factors. Predictors related to peritoneal metastasis of type IV GC were analyzed by multivariate Cox regression analysis. Borrmann type IV gastric cancer was associated with more advanced clinicopathological features at diagnosis than the other Borrmann type GC. Of the 159 patients with Borrmann type IV GC, the median OS was 23 months. The number of patients with peritoneal metastasis was 43, accounted for 27.0% of all the patients and 87.8% of the patients with distant metastasis. Multivariate analyses revealed lymph node metastasis to be independent prognostic factor for survival in Borrmann type IV GC patients. pN3b and tumor size > 50 mm showed to be risk factors for peritoneal metastasis. Borrmann type IV GC is an important independent prognostic factor. pN3b is an independent prognostic factor and a predictor of peritoneal metastasis in patients with Borrmann type IV GC.

Construction and validation of an immune-related genes prognostic index (IRGPI) model in colon cancer.

Though immunotherapy has become one of the standard therapies for colon cancer, the overall effective rate of immunotherapy is very low. Constructing an immune-related genes prognostic index (IRGPI) model may help to predict the response to immunotherapy and clinical outcomes. Differentially expressed immune-related genes (DEIRGs) between normal tissues and colon cancer tissues were identified and used to construct the co-expression network. Genes in the module with the most significant differences were further analyzed. Independent prognostic immune-related genes (IRGs) were identified by univariate and multivariate cox regression analysis. Independent prognostic IRGs were used to construct the IRGPI model using the multivariate cox proportional hazards regression model, and the IRGPI model was validated by independent dataset. ROC curves were plotted and AUCs were calculated to estimate the predictive power of the IRGPI model to prognosis. Gene set enrichment analysis (GSEA) was performed to screen the enriched KEGG pathways in the high-risk and low-risk phenotype. Correlations between IRGPI and clinical characteristic, immune checkpoint expression, TMB, immune cell infiltration, immune function, immune dysfunction, immune exclusion, immune subtype were analyzed. Totally 680 DEIRGs were identified. Three independent IRGs,NR5A2, PPARGC1A and LGALS4, were independently related to survival. NR5A2, PPARGC1A and LGALS4 were used to establish the IRGPI model. Survival analysis showed that patients with high-risk showed worse survival than patients in the low-risk group. The AUC of the IRGPI model for 1-year, 3-year and 5-year were 0.584, 0.608 and 0.697, respectively. Univariate analysis and multivariate cox regression analysis indicated that IRGPI were independent prognostic factors for survival. Stratified survival analysis showed that patients with IRGPI low-risk and low TMB had the best survival, which suggested that combination of TMB and IRGPI can better predict clinical outcome. Immune cell infiltration, immune function, immune checkpoint expression and immune exclusion were different between IRGPI high-risk and low-risk patients. An immune-related genes prognostic index (IRGPI) was constructed and validated in the current study and the IRGPI maybe a potential biomarker for evaluating response to immunotherapy and clinical outcome for colon cancer patients.

A pyroptosis-related gene model and its correlation with the microenvironment of lung adenocarcinoma: A bioinformatics analysis and experimental verification.

Background: Non-small cell lung cancer, comprising lung adenocarcinoma (LUAD) and lung squamous cell carcinoma, is one of the leading causes of cancer-related mortality. Pyroptosis is a new form of programmed cell death involved in cancer development. The relationship between LUAD and pyroptosis is unclear. This research aims to investigate this relationship and develop a stratified clinical model based on pyroptosis-related genes (PRGs). Methods: We analyzed the data of LUAD from The Cancer Genome Atlas (TCGA) and evaluated the expression of 48 PRGs to identify the differentially expressed genes. Then, constructing the risk model using the least absolute shrinkage and selection operator and the Cox regression method to find the gene signatures. The functional enrichment, immune cell infiltration, tumor mutational burden (TMB), and expression of immune checkpoints were compared to investigate the potential mechanism. The IC50 of common drugs was evaluated and compared. The inflammasome activation assay and lactate dehydrogenase (LDH) assay of NLR-family CARD-containing protein 4 (NLRC4) were also performed to confirm the role of pyroptosis in LUAD. Results: The pyroptosis-related model accurately predicted the prognosis of patients with LUAD, with the low-risk group exhibiting a higher survival probability. The risk score was an independent prognostic factor for survival. The stratified patients exhibited distinct tumor microenvironments, TMB, and drug sensitivity. The validation experiments of NLRC4 confirmed its role in inducing pyroptosis via promoting IL-1 maturation. Conclusion: PRGs regulated the tumor microenvironment and influenced the outcome of LUAD. NLRC4 may function as a hub gene in the process of LUAD.

Carotid space involvement is a prognostic factor and marker for induction chemotherapy in patients with nasopharyngeal carcinoma

ObjectivesThe carotid space is an integral part of the parapharyngeal space, with ambiguous prognostic value for patients with nasopharyngeal carcinoma (NPC). This study aimed to investigate the prognostic significance of carotid space involvement (CSI) and propose a treatment strategy. Materials and methodsThis retrospective study enrolled 792 patients with biopsy-confirmed, non-distant metastatic NPC staged by magnetic resonance imaging before treatment. We used multivariable Cox regression models and Kaplan–Meier methods to assess the association between the variables and survival outcomes. A matched-pair method (1:1) was used to compare the survival differences between the patients with CSI treated with induction chemotherapy (ICT)and that of those who were not. ResultsThe incidence rate of CSI was 21.7 % (172/792). Multivariate analysis revealed that CSI was not an independent prognostic factor for survival outcomes in the 792 patients with NPC; however, the Chi-square test showed a different distribution of treatment strategies with ICT for patients with and without CSI. After stratification by ICT, CSI was an independent prognostic factor for overall survival (OS) (p = 0.049) in patients without ICT, but not for distant metastasis-free, local recurrence-free, or progression-free survival (p˃0.05). Additionally, ICT improved OS in patients with CSI (hazard ratio, 0.42; p = 0.019). Matched pair analysis showed that patients with CSI gained prolonged OS from ICT compared with the non-ICT group (88.4 % vs 69.4 %, p = 0.028). ConclusionCSI was an independent negative prognostic factor for OS in patients with NPC without ICT and might be an imaging marker for identifying eligible candidates for ICT.

Prognosis of mucinous colon cancer is determined by histological biomarkers rather than microsatellite instability.

The prognostic value of microsatellite instability (MSI), as well as other histological characteristics such as lymphovascular invasion (LI), perineural invasion (PNI) and extramural vascular invasion (EMVI), is unclear in colorectal mucinous carcinoma (MC). This study aims to determine the relevance of these factors in MC patients and analyses the role of MSI in stage III MC patients treated with adjuvant chemotherapy. A cohort of 650 patients diagnosed with stages I-IV colonic MC from 2000 to 2010 was selected from PALGA, the nationwide Dutch pathology databank. Histopathology was revised and mismatch repair (MMR) status determined. Univariate and multivariate survival analyses were performed. Deficient MMR (dMMR) was found in 33% of MCs and correlated with female gender and right-sidedness, but also with lower tumour stage (stages I/II: 73.2 versus 47%; P < 0.0001) and the absence of EMVI (9.7 versus 23.7%; P < 0.0001) and PNI (5.6 versus 12.7%; P=0.005). On univariate analysis OS was better for dMMR MC than for proficient MMR (pMMR) MC (median OS of 9.7versus 5.0 years; P=0.009), but MMR status was no longer a relevant prognostic factor on multivariate analysis [hazard ratio (HR)=0.91, 95% confidence interval (CI)=0.70-1.18]. Stage III MC patients benefited from adjuvant chemotherapy, and dMMR status was associated with better OS in this group (HR=0.35, 95% CI=0.13-0.94). EMVI, LI and PNI, but not MMR, status are independent prognostic factors for survival in MC patients. Stage III MC patients benefit from adjuvant chemotherapy and dMMR status is associated with improved survival when adjuvant chemotherapy is given.

High HOXA9 gene expression predicts response to chemotherapy and prognosis of high-grade serous ovarian cancer patients.

High-grade serous ovarian cancer (HGSOC) is a deadly malignancy. Homeobox protein A9 (HOXA9) is linked with serous papillary histotype differentiation, and inappropriate HOXA9 expression is a step in ovarian cancer that induces aberrant differentiation. This study aimed to reveal the significance of HOXA9 in HGSOC. HOXA9 mRNA and protein expression were examined by quantitative PCR and immunohistochemistry, respectively. The chi-square test was used to evaluate associations between HOXA9 expression and clinical characteristics. The prognostic value of HOXA9 was calculated by the Kaplan-Meier method. The Kaplan-Meier Plotter database was used to assess the prognostic value of HOXA9. The mRNA and protein expression of HOXA9 were significantly upregulated in chemotherapy-resistant HGSOC compared with chemotherapy-sensitive HGSOC. The chi-square test showed that high HOXA9 expression was significantly related with grade, clinical stage, and residual disease. High HOXA9 expression was significantly associated with poor prognosis. The Kaplan-Meier Plotter database further confirmed these results. Cox hazard regression showed that high HOXA9 expression was an independent prognostic factor for survival in HGSOC patients. This study showed that HOXA9 expression was associated with chemotherapy resistance and poor outcomes in HGSOC patients. High HOXA9 expression might be a prognostic indicator for HGSOC.

Efficacy of tocilizumab therapy in severe COVID-19 pneumonia patients and determination of the prognostic factors affecting 30 days mortality

Objective: In coronavirus disease – 19 (COVID-19) patients, cytokine storm develops due to the increase of pro-inflammatory cytokines. Tocilizumab (TCZ), has been used in the treatment of COVID-19 patients and successful results have been obtained. The aim of this study was to determine the efficacy of TCZ and also investigate the prognostic factors affecting the success of treatment and mortality in COVID-19 patients treated with TCZ. Patients and Methods: Between March 2020 and August 2021, a total of 326 confirmed severe COVID-19 pneumonia patients, treated in the intensive care unit, were included in the study. Results: The mean age of the patients was 63.02±11.58 years, and 203 (62.3%) of the patients were male. Patients treated with TCZ therapy had a longer survival time compared with the standard therapy (p=0.012). It was found that type of respiratory support (HR:2.19, CI:1.10-4.36, p=0.025) and hyperlactatemia on the day of TCZ therapy admission (HR:2.93 CI:1.53-5.64, p=0.001) were the significant and independent prognostic factors of survival in severe COVID-19 pneumonia patients treated with TCZ. Conclusion: Tocilizumab therapy improved 30-days survival in critically ill COVID-19 pneumonia patients. Also, among the patients treated with TCZ, types of respiratory support and hyperlactatemia on the day of TCZ admission were the independent prognostic factors.

A composite indicator of derived neutrophil-lymphocyte ratio and lactate dehydrogenase correlates with outcomes in pancreatic carcinoma patients treated with PD-1 inhibitors.

There are currently no established biomarkers that can predict whether advanced pancreatic carcinoma (PC) patients would benefit from immune checkpoint inhibitors (ICIs). Our study investigated whether the pretreatment composite biomarker of derived neutrophil-lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) can be used as a reliable prognostic factor for the survival of PC patients receiving PD-1 inhibitor therapy. Patients with advanced PC treated with PD-1 inhibitors at a single center from September 2015 to September 2020 were included. The high levels of dNLR (≥3) and LDH (≥250 U/L) were considered to be risk factors. Based on these two risk factors, patients in this study were categorized into two risk groups: the good dNLR-LDH group, without risk factors, and the intermediate/poor dNLR-LDH group, with one to two risk factors. Overall survival (OS) and progression-free survival (PFS) served as this study's primary and secondary endpoints. Cox regression models were used to identify independent prognostic factors for survival benefit. There were 98 patients in our study. The good group included 61 (62.2%) patients and the intermediate/poor group included 37 (37.8%). The overall patients with PC who received immunotherapy had a median OS of 12.1 months, and the good dNLR-LDH group had a significantly longer OS compared with the intermediate/poor dNLR-LDH group (44.2 vs. 6.4 months; p < 0.010); median PFS was 3.7 and 2.5 months (p = 0.010). The number of metastatic sites >2 and immunotherapy as third-line or later was associated with worse PFS, and the line of immunotherapy and the dNLR-LDH indicator were independent prognostic factors for OS, according to multivariate analysis. The pretreatment composite biomarker of dNLR and LDH can be used as a prognostic biomarker in patients with advanced PC treated with PD-1 inhibitors.

Pulmonary function tests reveal unrecognised lung dysfunction and have independent prognostic significance in patients with systemic AL amyloidosis

Background Lung involvement in AL amyloidosis is not very common, but post-mortem data and retrospective studies suggest it is likely underrecognized. Aim To perform a comprehensive evaluation of lung function with pulmonary function tests (PFTs) in patients with newly diagnosed AL amyloidosis. Methods A prospective, non-interventional study of 139 consecutive patients with newly diagnosed AL amyloidosis. Results PFTs indicated normal breathing physiology in 68% of patients, obstructive in 9% and restrictive in 23%; the latter was associated with worse survival (28.6 vs 76 months for obstructive/normal physiology, p = 0.002) and remained significant after adjustment for Mayo stage and abnormal chest-CT. Forced vital capacity <80% of predicted value, forced expiratory volume <80% of predicted value, and carbon monoxide diffusion capacity <70% were independently associated with poorer survival. Respiratory muscle strength (as assessed by maximal expiratory (Pe) and inspiratory (Pi) pressure) was affected in most patients (64% had Pi < 55% and 57% had Pe < 70% of predicted values). Pe% was an independent prognostic factor for survival (HR: 0.984 per 1% unit increase, p = 0.007). Conclusions Pulmonary dysfunction, as assessed with PFTs, is common and underrecognized in patients with systemic AL amyloidosis, with significant prognostic and potentially therapeutic implications, independent of the degree of cardiac dysfunction or chest-CT findings.

Pre-Treatment Hemoglobin Concentration and Absolute Monocyte Count as Independent Prognostic Factors for Survival in Localized or Locally Advanced Prostate Cancer Patients Undergoing Radiotherapy.

The prognostic value of inflammatory indices, such as the absolute monocyte count (AMC), has been a subject of interest in recent prostate cancer (PCa) studies, while hemoglobin concentration (HGB) has been recognized as a survival factor in castration-resistant metastatic prostate cancer, but its value remains unclear in localized diseases. The aim of this study was to test the prognostic value of these two simple and inexpensive biomarkers for survival and was based on a cohort of 1016 patients treated with primary radiotherapy and androgen deprivation therapy for localized or locally advanced intermediate- or high-risk PCa. Complete survival data were available for all cases and were based on the National Cancer Registry, with a median observation time of 120 months (Interquartile Range (IQR) 80.9–144.7). Missing blood test data were supplemented using the Nearest Neighbor Imputation, and the Cox Proportional Hazards Regression model was used for analysis. The median age was 68.8 years (IQR 63.3–73.5). The five-year overall survival was 82.8%, and 508 patients were alive at the time of analysis. The median time between blood tests and the first day of radiotherapy was 6 days (IQR 0–19). HGB (p = 0.009) and AMC (p = 0.003) were independent prognostic factors for survival, along with age, Gleason Grade Group, clinical T stage and maximum prostate-specific antigen concentration. This study demonstrates that HGB and AMC can be useful biomarkers for overall survival in patients treated with radiotherapy for localized intermediate- or high-risk PCa.

Ultra-Hypofractionated Stereotactic Body Radiotherapy for Localized Prostate Cancer: Clinical Outcomes, Patterns of Recurrence, Feasibility of Definitive Salvage Treatment, and Competing Oncological Risk.

A cohort of 650 patients treated for localized prostate cancer (PCa) with CyberKnifeTM ultra-hypofractionated radiotherapy between 2011 and 2018 was retrospectively analyzed in terms of survival, patterns of failure, and outcomes of second-line definitive salvage therapies. The analysis was performed using survival analysis including the Kaplan–Meier method and Cox regression analysis. At a median follow-up of 49.4 months, the main pattern of failure was local–regional failure (7.4% in low-, and 13% in intermediate/high-risk group at five years), followed by distant metastases (3.6% in low-, and 6% in intermediate/high-risk group at five years). Five-year likelihood of developing a second malignancy was 7.3%; however, in the vast majority of the cases, the association with prior irradiation was unlikely. The 5-year overall survival was 90.2% in low-, and 88.8% in intermediate/high-risk patients. The independent prognostic factors for survival included age (HR 1.1; 95% CI 1.07–1.14) and occurrence of a second malignancy (HR 3.67; 95% CI 2.19–6.15). Definitive local salvage therapies were feasible in the majority of the patients with local–regional failure, and uncommonly in patients with distant metastases, with an estimated second-line progression free survival of 67.8% at two years. Competing oncological risks and age were significantly more important for patients’ survival compared to primary disease recurrence.

Prognostic Ability of Tumor Budding Outperforms Poorly Differentiated Clusters in Gastric Cancer.

Simple SummarySmall clusters of tumor cells at the invasion front of the tumor, known as “tumor budding” and larger clusters of cells, known as “poorly differentiated clusters”, are well known histological parameters to assess the outcome of colorectal cancer. However, their prognostic value for gastric cancer is less well investigated and controversial based on the studies conducted so far. In our retrospective study, we investigated the prognostic power of these two entities in a large cohort of gastric cancer patients. Our results demonstrate that tumor budding is an independent prognostic factor determining overall survival in gastric cancer, especially in intestinal type adenocarcinomas. In addition, budding can also predict the risk of lymph node metastases. However, although the trend is similar for poorly differentiated clusters, their predictive value is lower and they have not been shown to be an independent prognostic factor of survival in gastric cancer.The prognostic value of histological phenomena tumor budding (TB) and poorly differentiated clusters (PDCs) have been less studied in gastric cancer (GAC) and the data provided so far are controversial. In our study, 290 surgically resected GAC cases were evaluated for TB according to the criteria of International Tumor Budding Consensus Conference (ITBCC) and PDC, and both parameters were scored on a three-grade scale as described for colorectal cancer previously (0: Grade0, 1–4: Grade1, 5–9: Grade2 and ≥10: Grade3) and classified as low (Grade0–2) and high (Grade3) TB/PDC. High TB/PDC was associated with diffuse-type morphology, higher pT status, incomplete surgical resection, poor tumor differentiation and perineural and lymphovascular invasion. Multivariable survival analyses have shown an independent prognostic role of high TB with poorer overall survival in the total cohort (p = 0.014) and in intestinal-type adenocarcinomas (p = 0.005). Multivariable model revealed high TB as an independent predictor for lymph node metastasis in both the total cohort (p = 0.019) and in the intestinal type adenocarcinomas (p = 0.038). In contrast to tumor budding, no significant association was found between PDC and the occurrence of lymph node metastasis and tumor stage and even survival. In conclusion, tumor budding is an independent prognostic factor of survival in gastric cancer, especially in intestinal-type adenocarcinomas.